The conformations in aqueous solution at physiological pH and temperature of enkephalins and their analogs will be determined using absorption spectroscopy and circular dichroism. The main features that will be determined are: 1) the existence, if any, of ordered back-bone structures (S, or other, bends); 2) the relative position of aromatic side-chains; 3) the extent of intra- and/or intermolecular hydrogen bonding of the hydroxyl proton on the tyrosyl residue. With this data any conformation-activity correlations will be deduced. These experiments will be supplemented by calculations of conformational energies using branch-chain rotational isomeric state theory. These calculations of conformational energies using branch-chain rotational isomeric state theory. These calculations will allow a determination of any confirmations of significantly lower energy and, lacking that, give the percentage of molecules in those conformations that are attainable at body temperature. In vitro testing of the binding capacity of these molecules to brain homogonates and in vivo testing of analgesic activity will be compared to distinguish between these two functions. Results will be compared to known conformations of morphine and its analogs in solution.